This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Background: Muscle wasting is a common feature of chronic alcohol consumption and AIDS. Despite significant improvement in control of HIV-infection using highly active anti-retroviral therapy, AIDS wasting syndrome, with the resulting decline in body cell mass, remains a major cause of morbidity and mortality. We have shown that chronic alcohol administration accelerates progression and exacerbates the severity of muscle wasting associated with simian immunodeficiency virus (SIV) infection by altering the balance between protein anabolic and catabolic mechanisms. This study examines the endocrine and anabolic response to feeding in alcohol-treated animals prior to SIV infection and during the initial asymptomatic phase of infection and the added burden imposed by antiretroviral therapy (ART). Methods: In vivo rates of muscle protein synthesis were determined following feeding of a nutritionally and calorically controlled diet. Muscle expression of the rate-controlling molecular mechanisms involved in both synthetic (eukaryotic initiation factors, myostatin) and degradation (ubiquitin-proteasome) pathways, and circulating and tissue levels of recognized endocrine (IGF-I, GH, insulin &testosterone) nutritional (amino acids) and immune (pro-inflammatory cytokines) modulators of muscle mass will be measured. Results/Discussion: Studies have been conducted in all 8 SIV infected animals to assess neuroendocrine response to feeding and metabolic response following 12 weeks of ART. Alcohol treated SIV-infected animals showed marked decrease in testosterone and glucagon like peptide levels following feeding. In addition, chronic alcohol increased bone turnover during the ART period accentuating the loss in bone mineral content. Our findings indicate that ART increases bone osteoblastic activity shortly after its initiation and suggest that chronic alcohol accelerates detrimental side-effects of ART therapy by altering the balance between bone formation and resorption potentially enhancing loss of bone mineral mass and decreasing bone density. Moreover, the decreased testosterone levels suggest an important role for neuroendocrine mechanisms in these CBA-mediated effects.